In the proposed research four groups of pregnant women are studied prospectively throughout gestation and postpartum. They comprise lean and obese nondiabetic and diabetic subjects. The effects of obesity and/or diabetes on basal plasma concentrations of lipids, lipoproteins and lipid composition of lipoproteins are assessed together with measurements of ketone bodies and amino acids and glucoregulatory hormones, insulin and glucagon in each trimester of pregnancy and postpartum. In addition, plasma insulin and glucagon responses to oral glucose and amino acids are assessed. Departures of obese, diabetic and obese diabetic women from defined norms of the lean control group are, in turn, related to neonatal metabolic parameters, development and complication at birth. Maternal metabolic profiles are correlated with the metabolic control marker, Hemoglobin AIc. Specific patterns of HLA histocompatibility antigens are sought in problem pregnacies in both mother and fetus and are extended to family members. The prospective study serves to delineate factors of a metabolic, hormonal or genetic type that may distinguish obese and/or diabetic women from uncomplicated pregnancies and help prognosticate potential fetal abnormalities.